Pipeline Insight: Osteoporosis - Intermittent Dosing and Multiple Indications Drive Market Growth

SUMMARY

Osteoporosis therapy is the focus of attention of significant R&Dactivity, with drugs in development both in existing classes offering advantagesover marketed products and novel drugs exploiting genomics programs and a deeperunderstanding of bone biology.

SCOPE OF THE REPORT

• Epidemiology of osteoporosis in the seven major markets by diseaseseverity, identification of niche populations and unmet needs
• Detailed profiles of drugs in Phase II and above - clinical data, patientpotential, marketing factors, satisfaction of unmet needs
• Primary research with key osteoporosis opinion leaders providing insighton future market entrants and innovative R&D projects in the diseasearea
• Global sales forecasts for key pipeline drugs, currently marketed productsand classes

REPORT HIGHLIGHTS

Novel bisphosphonates, Zometa and Boniva, with innovative dosing regimens anddelivery methods, will lead growth in the osteoporosis market; R&Dosteoporosis drugs will reach sales of $4.7 billion by 2011.

Driven by newmarket leader Evista, which will lead Pfizer's lasofoxifene and Wyeth'sbazedoxifene by targeting multiple indications, the SERMs drug class will bevalued at $4.2 billion by 2011.

The early-stage pipeline consists largely ofdrug candidates in new therapeutic classes, in particular cathepsin Kinhibitors, osteoprotegerin and calcilytics. While these drugs have thepotential to change the face of osteoporosis treatment in the long term,innovative approaches will likely be costly to patients, limiting potential.

KEY REASONS TO BUY THIS REPORT

• Validate internal forecasts against drug/class sales model and assessmarket potential for pipeline products
• Analyze competitive environment at time of product launch to inform beststrategy for market entry
• Highlight key R&D trends and company involvement in the market toinform licensing decisions and identify potential partners based on R&Dactivity

TABLE OF CONTENTS

CHAPTER 1 EXECUTIVE SUMMARY

• Scope of the analysis
• Datamonitor insight into the osteoporosis market
  • Innovative bisphosphonates, Zometa (zoledronate) and Boniva (ibandonrate), with their novel dosing regimens and delivery methods, will drive growth in the osteoporosis market, as sales will reach $10.4 billion by 2011
  • Driven by new market leader Evista (raloxifene), which will stay one step ahead of lead Pfizer's lasofoxifene and Wyeth's bazedoxifene by targeting multiple indications, the SERMs drug class will be valued at $4.2 billion by 2011
  • The osteoporosis early stage pipeline consists largely of drug candidates in new therapeutic classes, in particular cathepsin K inhibitors, osteoprotegerin and calcilytics. While these drugs have the potential to change the face of osteoporosis treatment in the long term, innovative approaches will likely be costly to patients, limiting potential
  • Summary
• Key metrics

CHAPTER 2 PATIENT POTENTIAL

• Definition of osteoporosis
  • Etiology of osteoporosis
• Epidemiology of osteoporosis
  • Methodological difficulties in assessing prevalence
  • Prevalence of osteoporosis and osteopenia in postmenopausal women
• Segmentation of osteoporosis
  • Prevalence of osteoporosis and osteopenia in men
  • Osteoporosis population forecast
  • Osteoporotic fractures, their implications and minor risk groups
  • Niche populations
• Unmet need in osteoporosis
  • Clinical unmet need

CHAPTER 3 R&D APPROACH

• Classification of pipeline products
  • Bisphosphonates
  • SERMs
  • Calcitonins
  • Parathyroid hormone and analogues
  • Hormone therapy
• Clinical trial design in osteoporosis
  • Clinical trial guidelines
  • Trial design and implementation in osteoporosis: the future?
  • Clinical trial endpoints in osteoporosis
  • Fracture rate
  • Changes in BMD
  • Biochemical markers of bone turnover
  • Changes in bone microarchitecture

CHAPTER 4 OSTEOPOROSIS PIPELINE ANALYSIS

• Pipeline overview
• Key companies involved in the osteoporosis pipeline
  • Novartis
  • GSK
  • Merck – a notable absentee
• Strategies for success in osteoporosis
  • Dosing variations in the bisphosphonate class
  • Multiple indications strategy in osteoporosis

CHAPTER 5 BISPHOSPHONATE LATE-STAGE DRUG ANALYSIS & FORECASTS

• Overview for the bisphosphonate class
  • Pipeline summary
  • Definition of current comparator therapy
• Comparative analysis
  • Bonviva (ibandronate)
  • Forecasts to 2011
• Zometa (zoledronate)
  • Forecasts to 2011
• Other late stage drugs
  • Minodronate
  • Apomine
  • Clodronate
• Comparison of key compounds in the bisphosphonate class
  • Unmet needs
  • Marketing strength
  • Comparative forecasts

CHAPTER 6 SERMS LATE-STAGE ANALYSIS AND FORECASTS

• Overview table
• Definition of current comparator therapy
• Comparative analysis
  • Lasofoxifene
  • Forecasts to 2011
• Bazedoxifene
  • Drug overview
  • Forecasts to 2011
• Other late stage drugs
  • Ospemifene
• Comparison of key compounds in the SERM class
  • Unmet needs
  • Marketing strength
  • Comparative forecasts

CHAPTER 7 CALCITONIN LATE-STAGE DRUG ANALYSIS AND FORECASTS

• Overview table
• Definition of current comparator therapy
  • Overview
• Comparative analysis
  • Fortical
  • Forecasts to 2011
• Other drugs in the calcitonin class
  • SMC021
  • rsCT

CHAPTER 8 PTH LATE-STAGE DRUG ANALYSIS AND FORECASTS

• Overview for PTH class
  • Definition of current comparator therapy
• Comparative analysis
  • Preos (rhPTH 1-84)
  • Satisfaction of unmet needs
• Forecasts to 2011
• Other drugs in the PTH class
  • Asahi teriparatide/PTH (1(34)
• Comparative forecasts

CHAPTER 9 'OTHER' DRUGS LATE STAGE ANALYSIS AND FORECASTS

• Overview
• Definition of current comparator therapy
• Comparative analysis
  • Strontium ranelate
• Forecasts to 2011
• Additional drugs in the 'other' class
  • Nitroflurbiprofen
  • Osteoprotegerin
  • SomataKine (IGF 9606)

CHAPTER 10 INNOVATIVE EARLY-STAGE PROJECTS

• Key phase I and preclinical compounds in osteoporosis
• Cathepsin K inhibitors
  • Novartis - AAE581
  • GSK - SB-462795
  • Merck/Celera
• Calcilytics
  • GSK/NPS – 423557
• Calcitonin
  • Nobex/Elan – Oratonin
• PTH
  • Unigene/GSK
• Src kinase inhibitors
  • Ariad
• PPAR gamma modulators
  • GSK/Bayer
• Vitronectin receptor antagonists
  • GSK – SB 273005
• Long-acting proteins
  • Human Genome Sciences
• Wyeth looking away from hormones to new horizons?
• Key research impacts on osteoporosis
  • Impacts of clinical trial issues

CHAPTER 11 OPINION LEADER TRANSCRIPTS

• Key opinion leader 1 - Belgium
  • Unmet needs
  • Pipeline
  • Novel drug targets
  • Clinical trial design
• Key opinion leader 2 – US
  • Unmet needs
  • Clinical trial design
• Key opinion leader 3 – US
  • Unmet needs
  • Pipeline
  • Novel drug targets
  • Clinical trial design
• Key opinion leader 4 – US
  • Unmet needs
  • Pipeline
  • Novel drug targets
  • Clinical trial design
• Contributing experts
• Bibliography
  • Epidemiology
  • Clinical trial data
• Report methodology

List of Tables

• Table 1: Key parameters of the osteoporosis market
• Table 2: Forecast key pipeline products in osteoporosis to 2011
• Table 3: Causes of secondary (Type III) osteoporosis
• Table 4: WHO classification of osteoporotic bone loss
• Table 5: Epidemiology overview of osteoporosis
• Table 6: Prevalence of osteopenia and osteoporosis in postmenopausal women across the seven major markets, 2003
• Table 7: Prevalence of osteopenia and osteoporosis in men over 50 in the seven major markets, 2003
• Table 8: Estimated forecast of the osteoporosis and osteopenia populations over 50 years in the seven major markets, 000s, 2003(11
• Table 9: Prevalence of vertebral fractures in men and women over 50 in the seven major markets, 2003
• Table 10: Overview of currently marketed bisphosphonates indicated for use in osteoporosis
• Table 11: Overview of currently marketed SERMs indicated for use in osteoporosis
• Table 12: Overview of currently marketed SERMs indicated for use in osteoporosis
• Table 13: Quantitative measures used for clinical efficacy endpoints in osteoporosis
• Table 14: R&D pipeline in osteoporosis, 2003
• Table 16: Key bisphosphonate products in late-stage R&D pipeline 2003
• Table 17: Defining the gold standard: key clinical trial results for Fosamax
• Table 18: Dose ranging study results for 20mg and placebo with ibandronate, % change from baseline
• Table 19: Results at 2 and 3-years in study comparing 3-monthly i.v. ibandronate, and daily oral alfacalcidol, % BMD relative to baseline, 2003
• Table 20: Novartis's HORIZON trial design, 2003
• Table 21: Difference between two treatment groups at 48 months, mean % change in BMD from baseline
• Table 22: Global sales forecasts for the bisphosphonate class, 2003(11
• Table 23: Overview of the SERMs in late stage development for the prevention or treatment of osteoporosis
• Table 24: Evista: key facts
• Table 25: Global sales forecasts for the SERM class, 2003(11
• Table 26: Overview of the calcitonins in late stage development for the prevention or treatment of osteoporosis
• Table 27: Miacalcin: key facts
• Table 28: Global sales forecast for the calcitonin class, 2003(11
• Table 29: Summary of the PTH drugs in late stage development for osteoporosis
• Table 30: Forteo: key facts
• Table 31: Results of PATH trial, %, 2003
• Table 32: Global sales forecast for the PTH class, 2003(11
• Table 33: Summary of other late stage drugs in development for osteoporosis, 2003
• Table 34: Study population, design and end points.
• Table 35: PREVOS change in BMD results, % from baseline
• Table 36: STRATOS mean annual change in BMD, % from baseline
• Table 37: Drugs in phase I and preclinical development for osteoporosis, 2003

List of Figures

• Figure 1: Summary of osteoporosis pipeline by development phase, mechanism of action and company category, 2003
• Figure 2: Drug launches and events in the osteoporosis market from 2003
• Figure 3: Schematic of key current and pipeline drugs, their targets and their effect on bone formation and resorption
• Figure 4: Osteoporosis drugs and their overlap into other indications
• Figure 5: Prevalence of osteopenia and osteoporosis in postmenopausal women across the seven major markets, 2003
• Figure 6: Prevalence of osteopenia and osteoporosis in men over 50 in the seven major markets, 2003
• Figure 7: Prevalence of vertebral fractures in men and women over 50 in the seven major markets, 2003
• Figure 8: Clinical unmet needs in osteoporosis
• Figure 9: Boniva satisfaction of unmet needs in osteoporosis – comparative analysis vs. Fosamax
• Figure 10: Global market forecast and events for Boniva, 2005(2011
• Figure 11: Zometa satisfaction of unmet needs – comparative analysis vs. Fosamax
• Figure 12: Global market forecast and events for Zometa to 2011
• Figure 13: Comparison of key compounds in the bisphosphonate class currently in late stage development, 2003
• Figure 14: Comparative analysis of lasofoxifene and Evista
• Figure 15: Global market forecast and events for lasofoxifene to 2011
• Figure 16: Bazedoxifene satisfaction of unmet needs – comparative analysis vs. Evista
• Figure 17: Global market forecasts and events for bazedoxifene to 2011
• Figure 18: Comparison of key compounds in the SERM class currently in late stage development, 2003
• Figure 19: Fortical satisfaction of unmet needs – comparative analysis vs. Miacalcin
• Figure 20: Global market forecasts and events for Fortical to 2011
• Figure 21: Preos satisfaction of unmet needs – comparative analysis vs. Forteo
• Figure 22: Global market forecast and events for Preos to 2011
• Figure 23: Protos satisfaction of unmet needs – comparative analysis with Fosamax
• Figure 24: Global market forecast and events for Protos to 2011